1-脱氧鞘脂的特性、功能及在相关疾病中的作用
Characteristics,functions,and roles of 1-deoxysphingolipids in related diseases
杨谋杰 1王俊楠 1邬慧贤 1金俊飞 1潘志雄1
作者信息
- 1. 桂林医学院附属医院 广西肝脏损伤与修复分子医学重点实验室,桂林 541001;桂林医学院附属医院 广西神经鞘脂代谢相关疾病基础研究重点实验室,桂林 541001;桂林医学院附属医院 肝胆胰外科实验室,桂林 541001;桂林医学院中美健康与疾病脂质研究中心,桂林 541001
- 折叠
摘要
鞘脂是细胞膜脂的重要组成部分,在多种疾病中起重要作用.当鞘脂合成路径被干扰时,鞘脂代谢重编程,导致合成产物转变为1-脱氧鞘脂(DoxSL).在梳理已有文献的基础上,介绍了DoxSL的生物合成、代谢及相关功能,特别是DoxSL在细胞毒性、神经突的影响及膜疏水性方面的作用.此外,DoxSL水平异常与多种人类疾病有关,丝氨酸含量降低会导致DoxSL病理性升高,而升高的DoxSL与糖尿病、非酒精性脂肪性肝病(NAFLD)以及遗传性感觉自主神经病 1 型(HSAN1)相关.DoxSL可用作预测糖尿病的生物标志物,参与NAFLD的肝细胞脂肪变性.丝氨酸棕榈酰转移酶亚基的突变导致DoxSL增加是形成HSAN1 的重要原因,故监测、调控DoxSL含量可能为临床相关疾病的诊断与治疗提供新思路.
Abstract
Sphingolipids are important components of cell membrane lipids and play an important role in many diseases.When the sphingolipid synthesis pathway is disturbed,sphingolipid metabolism is reprogrammed,resulting in the transformation of synthetic products into 1-deoxysphingolipid(DoxSL).This article introduces the biosynthesis,metabolism and related functions of DoxSL,with emphasis on the effects of DoxSL on cytotoxicity,neurite effect and membrane hydrophobicity.In addition,abnormal DoxSL level has been associated with a variety of human diseases,with lower serine level leading to pathological increases in DoxSL,and elevated DoxSL has been associated with diabetes,non-alcoholic fatty liver disease(NAFLD),and hereditary Sensory Autonomic Neuropathy type 1(HSAN1).DoxSL can be used as a biomarker to predict diabetes,hepatocyte steatosis involved in NAFLD,and the increase of DoxSL caused by mutation of serine palmitoyl transferase subunit is an important reason for the formation of HSAN1.Monitoring and regulating DoxSL content may provide new ideas for the diagnosis and treatment of clinically related diseases.This review will briefly discuss the characteristics and functions of DoxSL and its role in the occurrence and development of related diseases.
关键词
1-脱氧鞘脂/生物合成/糖尿病/非酒精性脂肪性肝病/遗传性感觉自主神经病1型Key words
1-deoxysphingolipid/biosynthesis/diabetes/non-alcoholic fatty liver disease/hereditary sensory autonomic neuropathy type 1引用本文复制引用
基金项目
国家自然科学基金(81960520)
广西科技厅中央引导地方科技发展资金项目(桂科ZY21195024)
广西自然科学基金重点项目(2020GXNSFDA238006)
桂林市漓江学者项目(第三批)(2022-5-07)
广西医学高层次骨干人才"139"计划(G202002005)
广西壮族自治区卫生健康委广西神经鞘脂代谢相关疾病基础研究重点实验室建设经费项目(ZJC2020005)
广西壮族自治区医疗卫生重点学科建设项目(2021-8-4-3)
桂林市科学研究与技术开发计划(20210102-1)
广西壮族自治区高等学校中青年教师科研基础能力提升项目(2023KY0504)
出版年
2024
NETL
NSTL
万方数据